The nucleus tractus solitarius (NTS), the ventrolateral medulla (VLM), the dorsal motor vagus nucleus (DMnX) and the locus coeruleus (LC) are catecholaminergic brainstem areas involved in ventilatory and cardiovascular responses to
hypoxia and
tyrosine hydroxylation is the rate limiting step of cathecholamine biosynthesis in the central nervous system. The aim of this study was to evaluate the effects of long-term
hypoxia on
tyrosine hydroxylase (TH) content in these different areas using a quantitative autoradiographic technique. Two experimental groups of rats were studied: Group I (9 males, 8 females) was submitted to normobaric
hypoxia (10% O2-90% N2) for 21 days and compared to 12 (6 males, 6 females) normoxic control rats (Group II). Coronal tissue sections from fresh-frozen rat brains, obtained along the caudo-rostral axis, were incubated in the presence of a TH
monoclonal antibody, and the reaction was revealed by a 35S-labelled secondary antibody. TH levels were quantified in the NTS, VLM, DMnX and LC by measuring optical density on autoradiographic films using an automatic image analyser system. Regional
antigen quantification was assessed by computer-assisted image analysis. Chronic
hypoxia led to
body weight decrease until day 5, haematocrit increase (65 +/- 2% vs. 44 +/- 2%, P < 0.01) and right ventricle
hypertrophy (35 +/- 0.5% vs. 23 +/- 0.1% of the weight of the two ventricles, P < 0.01). TH
protein contents expressed as percentage of controls were as follows. In males, in the rostral part of the NTS 132 +/- 9% (P < 0.02), in the caudal part of the NTS, 117 +/- 5% (P < 0.04). In female rats, the TH quantity reached a value of 124 +/- 4% (P < 0.01) in the rostral part and 126 +/- 6% (P < 0.01) in the caudal part of the NTS. In females, TH content was significantly increased in the VLM, 124 +/- 6%, P = 0.01, whereas in males there was only a non-significant trend to increase, 122 +/- 11%. In females, there was a significant increase in the DMnX, 127 +/- 9%, P = 0.05, whereas in males there was only a trend to increase, 120 +/- 5%. This study shows that long-term
hypoxia induces a persistent increase in TH
protein content both in the caudal and rostral part of the NTS, which are known to receive respectively chemo- and barosensory inputs, and in other catecholaminergic areas involved in baroreflex activity. Our data clearly demonstrate the implication of neurochemical mechanisms in the central relationship between chemo- and baroreflex which are responsible for changes in systemic arterial pressure and
oxygen partial pressure as required for maintaining an adequate
oxygen supply to the tissues.